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Zhang YH, Kenyon JL, Nicol GD: Phorbol ester-induced inhibition of potassium currents in rat sensory neurons requires voltage-dependent entry of calcium. J Neurophysiol. 2001 Jan;85(1):362-73.
The whole cell patch-clamp technique was used to examine the effects of protein kinase C (PKC) activation (via the phorbol ester, phorbol 12,13 dibutyrate, PDBu) on the modulation of potassium currents (I (K)) in cultured capsaicin-sensitive neurons isolated from dorsal root ganglia from embryonic rat pups and grown in culture. PDBu, in a concentration- and time-dependent manner, reduced I (K) measured at +60 mV by approximately 30% if the holding potential (V (h)) was -20 or -47 mV but had no effect if V (h) was -80 mV. The PDBu-induced inhibition of I (K) was blocked by pretreatment with the PKC inhibitor bisindolylmaleimide I and I (K) was unaffected by 4-alpha phorbol, indicating that the suppression of I (K) was mediated by PKC. The inhibition of I (K) by 100 nM PDBu at a V (h) of -50 mV was reversed over several minutes if V (h) was changed to -80 mV. In addition, intracellular perfusion with 5 mM bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) or pretreatment with omega-conotoxin GVIA or Cd (2+)-Ringer, but not nifedipine, prevented the PDBu-induced suppression of I (K) at -50 mV, suggesting that a voltage-dependent influx of calcium through N-type calcium channels was necessary for the activation of PKC. The potassium channel blockers tetraethylammonium (TEA, 10 mM) and 4-aminopyridine (4-AP, 3 mM and 30 microM) reduced I (K), but only TEA attenuated the ability of PDBu to further inhibit the current, suggesting that the I (K) modified by PDBu was sensitive to TEA. Interestingly, in the presence of 3 mM or 30 microM 4-AP, 100 nM PDBu inhibited I (K) when V (h) was -80 mV. Thus 4-AP promotes the capacity of PDBu to reduce I (K) at -80 mV. We find that activation of PKC inhibits I (K) in rat sensory neurons and that voltage-dependent calcium entry is necessary for the development and maintenance of this inhibition. |
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